• Bulletin of the Korean Chemical Society
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• v.28 no.12
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• pp.2203-2208
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• 2007

Three possible binding modes of cationic meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP) to d[(GCATATATGC)2] duplex were investigated by the molecular dynamics (MD) simulation. Among the three binding modes namely, “along the groove”, “across the groove” and “face on the groove”, the “across the groove” model exhibited the largest negative binding free energy and the DNA backbone remained as the B form. In this model, the molecular plain of the TMPyP tilts 45o with respect to the DNA helix axis and is largely exposed to the solvent. TMPyP was stabilized mainly by the interaction between the positively charged neighboring pyridinium moieties of TMPyP and negatively charged phosphate groups of DNA. The result obtained in this work by MD and the report (Jin, B. et al., J. Am. Chem. Soc. 2005, 127, 2417.) that the spectral properties of poly[d(A-T)2] bound TMPyP in the presence and absence of the minor groove binding drug 4',6- diamidino-2-phenylindole are similar, we propose that TMPyP bind across the minor groove of the AT rich- DNA.

• Bulletin of the Korean Chemical Society
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• v.34 no.10
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• pp.2895-2899
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• 2013

Direction of intercalation to DNA of the planar dipyrido[3,2-a:2',3'-c]phenazine ligands (dppz) of a bis-Ru(II) complex namely, $[Ru(1,10-phenanthroline)_2dipyrido[3,2-a:2^{\prime},3^{\prime}-c]phenazine]^{2+}$ linkered by a 1,3-bis(4-pyridyl)propane, was investigated by probing the behavior of 4',6-diamidino-2-phenylindole (DAPI) that bound deep in the minor groove. Bis-intercalation of DPPZ resulted in a little blue shift and hyperchromism in DAPI absorption band, and a large decrease in DAPI fluorescence intensity which accompined by an increase in the dppz emission intensity. Diminishing the intenisty of the positive induced circular dichroism (CD) and linear dichroism (LD) were also observed. These spectral changes indicated that insertion of dppz ligand caused the change of the binding mode of DAPI, which probably moved to the exterior of DNA from the minor groove and interacted with the phospghate groups of DNA by electrostatic interaction. At the surface of DNA, DAPI binds at the phosphate groups of DNA by electrostatic attraction. Consequently, this observation indicated that the dppz ligand intercalated from the minor groove.

• Journal of the Korean Chemical Society
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• v.42 no.1
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• pp.1-8
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• 1998

Molecular electrostatic potential (MEP) of the thiazole, relevant to the binding of lexitroposin that contains thiazole ring to the base pair of minor groove of DNA is obtained from the results of ab initio calculation. The geometry optimization for the two possible conformations of protonated thiazoles is performed with the aid of MNDO and ab initio calculations. The proton affinities are calculated at the 6-31G and 6-31G basis set for the optimized geometry. The proton affinities are also studied for various substituted thiazoles with the electron-donating and electron-withdrawing groups to estimate substituent effect on the proton affinity of thiazoles. It is found that the thiazole with nitrogen atom aligned inward to the DNA minor groove exhibit higher proton affinity and electron-donating substituents increase the proton affinity of thiazoles.ĀȀꃏ?⨀缾ĀȀ會ĀȀ?⨀ꖓĀĀȀ會ĀȀ僐?⨀聥ꖓĀĀȀ會ĀȀ꣐?⨀聐缾ĀȀ會ĀȀÑ?⨀ၑ缾ĀȀ會ĀȀ壑?⨀ꁑ缾ᨀĀꀏ會Āꀏ냑?⨀⡒缾᐀Āꀏ會Āꀏ࣒?⨀끒缾ᰀĀꀏ會Āꀏ惒?⨀ꁩꖓȀĀꀏ會Āꀏ룒?⨀⡪ꖓሀĀꀏ會Āꀏდ?⨀ᤐ돀삺?⨀塨?⨀飣?⨀돐룣?⨀偠잖⨀샣?⨀줏덐탣?⨀젏ꠏܞ
Ȍ蠀
ᥲ⴯

ͧ
Molecua及컲ࡔ
ȏᰗۊऀں
Molecular electrostatic potential (MEP) of the thiazole, relevant to the binding of lexitroposin that contains thiazole ring to the base pair of minor groove of DNA is obtained from the results of ab initio calculation. The geometry optimization for the two possible conformations of protonated thiazoles

• Journal of the Korean Chemical Society
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• v.51 no.1
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• pp.7-13
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• 2007

The oxazole plays an important role in the binding of lexitropsin to the guanine-cytosine base pair from minor groove of DNA. The geometry optimization is performed with DFT calculations for the two possible conformations of the protonated oxazole. The proton affinities are calculated at B3LYP level of theory with 6-31G* basis set for the optimized geometry. It is found that the proton affinites of the conformations in which the oxazole nitrogen is the protonation center are greater than that of the conformations in which the oxazole oxygen is the protonation center. This result is in good agreement with molecular electrostatic potential (MEP) contour map. The proton affinities are also studied for various substituted oxazoles with the electron-donating and -withdrawing groups to estimate substitutent effect on the proton affinity at the hydrogen bonding site of the oxazoles. it is shown that the electron-donating substituents increase the proton affinity of oxazole, while the electron-withdrawing substituents decrease it.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.562-570
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• 2021

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

• KIEE International Transactions on Electrophysics and Applications
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• v.4C no.4
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• pp.145-148
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• 2004

In this study, a DNA chip with a microelectrode array was fabricated using microfabrication technology. Several probe DNAs consisting of mercaptohexyl moiety at their 5' end were immobilized on the gold electrodes by a DNA arrayer. Then target DNAs were hybridized and reacted with Hoechst 33258, which is a DNA minor groove binder and electrochemically active dye. Linear sweep voltammetry or cyclic voltammetry showed a difference between target DNA and control DNA in the anodic peak current values. It was derived from Hoechst 33258 and concentrated at the electrode surface through association with the formed hybrid. This suggested that this DNA chip could recognize the sequence specific genes.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.62-66
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• 2010

Benzopyrene is known to be one of the most powerful carcinogens which can build intercalated motif between base pairs in damaged DNA. The dimension of benzopyrene itself is much bigger than any of the DNA bases and thus the question whether the lesion of some base pair by insertion of benzopyrene can happen with or without a dramatic distortion of the helical structure is a highly interesting theme. In this work we used a molecular mechanics simulation using AMBER program package to go into the conformational characteristics. The condition of the insertion process of the benzopyrene motif from minor groove of the starting structure between the base pairs in the internal area of double helix was investigated using the molecular dynamics simulation at elevated temperature.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.67-74
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• 2010

Some of the benzopyrene (BP)-DNA adduct are known to build intercalated motif between flanking base pairs in damaged DNA depending on the structural condition. The size of benzopyrene itself is definitely not comparable with any of the DNA bases and thus the question whether the lesion of some base pair by insertion of benzopyrene can happen with or without a dramatic distortion of the helical structure is a highly interesting theme. In this work we used a molecular dynamics simulation based on the theory of molecular mechanics. The specific consequences about the structural properties of the intercalated structures and benzopyrene motif in minor groove of the double helix are deduced after 5 ns simulation time.

• Journal of the Korean Magnetic Resonance Society
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• v.8 no.2
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• pp.96-107
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• 2004

We prepared two oligonucleotides containing same base pairing, but different base sequence in the middle region, d(CGAATTCG) and d(CGTATACG). NMR and UV absorbance data represented that such variation in base sequence could cause a significant difference in melting temperature and dynamics between d(CGAATTCG)$_2$ and d(CGTATACG)$_2$ duplexes, which are regarded to be associated with the stacked structure and the width of the minor groove of them. The latter showed poor stability compared to the former, because of poor stacking of bases. And berenil could bind to the minor groove of d(CGAATTCG)$_2$ which is relatively narrow, more strongly than d(CGTATACG)$_2$ and this gave rise to large improvement in thermal stability of the d(CGAATTCG)$_2$ duplex, compared to d(CGTATACG)$_2$.

• Bulletin of the Korean Chemical Society
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• v.34 no.7
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• pp.2117-2124
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• 2013

The binding properties and sequence selectivities of ${\Delta}{\Delta}$- and ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ (bip = 4,4'-biphenylene (imidazo [4,4-f][1,10]phenanthroline) complexes with $poly[d(A-T)_2]$ and $poly[d(G-C)_2]$ were investigated using conventional spectroscopic methods. When bound to $poly[d(A-T)_2]$, a large positive circular dichroism (CD) spectrum was induced in absorption region of the bridging moiety for both the ${\Delta}{\Delta}$- and ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ complexes, which suggested that the bridging moiety sits in the minor groove of the polynucleotide. As luminescence intensity increased, decay times became longer and complexes were well-protected from the negatively charged iodide quencher compared to that in the absence of $poly[d(A-T)_2]$. These luminescence measurements indicated that Ru(II) enantiomers were in a less polar environment compared to that in water and supported by minor groove binding. An angle of $45^{\circ}$ between the molecular plane of the bridging moiety of the ${\Delta}{\Delta}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ complex and the local DNA helix axis calculated from reduced linear dichroism ($LD^r$) spectrum further supported the minor groove binding mode. In the case of ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ complex, this angle was $55^{\circ}$, suggesting a tilt of DNA stem near the binding site and bridging moiety sit in the minor groove of the $poly[d(A-T)_2]$. In contrast, neither ${\Delta}{\Delta}$-nor ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ complex produced significant CD or $LD^r$ signal in the absorption region of the bridging moiety. Luminescence measurements revealed that both the ${\Delta}{\Delta}$- and ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ complexes were partially accessible to the $I^-$ quencher. Furthermore, decay times became shorter when bis-Ru(II) complexes bound to $poly[d(G-C)_2]$. These observations suggest that both the ${\Delta}{\Delta}$- and ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ complexes bind at the surface of $poly[d(G-C)_2]$, probably electrostatically to phosphate group. The results indicate that ${\Delta}{\Delta}$- and ${\Lambda}{\Lambda}-[{\mu}-Ru_2(phen)_4(bip)]^{4+}$ are able to discriminate between AT and GC base pairs.